In order to investigate the causes of chest pain in patients found to have angiographically normal coronary arteries during cardiac catheterization) cardiac sensitivity to catheter manipulation, pacing at various stimulus intensities, and intracoronary injection of contrast media were examined in several groups of patients undergoing cardiac catheterization. Right heart (especially right ventricular) catheter manipulation and pacing, and intracoronary contrast media injection, provoked chest pain typical of that previously experienced in 29/36 (81%) of patients with chest pain and angiographically normal coronary arteries and 15/33 (46%) symptomatic patients with hypertrophic cardiomyopathy. In contrast, only 2/33 (6%) symptomatic patients with coronary artery disease experienced their typical chest pain with these sensitivity tests (P<0.001). None of the 10 patients with valvular heart disease but without the chest pain syndrome, experienced any sensation whatsoever with these tests. Thus, patients who have chest pain despite angiographically normal arteries have abnormal cardiac sensitivity to a variety of stimuli, which may be of causal importance to the chest pain syndrome or may contribute to their perception of ischemia-induced pain. The same phenomenon was also commonly seen in symptomatic patients with hypertrophic cardiomyopathy. Whether this phenomenon represents abnormal activation of pain receptors within the heart, or abnormal processing of visceral afferent neural impulses in the peripheral or central nervous system is unknown.